Samuel Pahlsson and Antoine Vermette also scored for Columbus, and Steve Mason was sensational in net with 32 saves.
The Blue Jackets avenged a 7-2 loss to Pittsburgh on Dec. 4, when Sidney Crosby had two goals for the Penguins. At the Consol Energy Center, Crosby was missing for the 14th straight game.
The Penguins added center Chris Kunitz to an injury list that already includes Crosby (concussion) and Evgeni Malkin (knee). Kunitz, third on the team in goals, has a lower-body injury and is day to day.
No Penguins player in the lineup had more than 10 goals.
Tyler Kennedy spoiled Mason's shutout bid with a power-play goal in the third period to make it 3-1. But by then, it was too late for the decimated Penguins.
Crosby is skating on his own away from the team and has kept in touch with Pittsburgh's trainer. The Penguins clearly won't rush his return - but it's clear they need him.
They lost their second straight game with Crosby and Malkin out. Malkin was lost last week to two torn ligaments in his right knee. The Penguins are faced with the grim possibility of playing without their top two stars the rest of the season.
There was no sympathy from Columbus. The Blue Jackets won their third straight game as they make a late push for the eighth and final playoff spot in the Western Conference. Their offense could be heating up at the right time, as Columbus has scored at least three goals in four straight games.
Nash scored on a one-timer from the right circle for a 1-0 lead in the first. He dropped to one knee to send his 24th goal of the season past Marc-Andre Fleury, who was tied for second in the NHL with 25 wins.
The Blue Jackets built a 3-0 lead in the second to silence the 195th straight sellout crowd at the sparkling Consol Energy Center.
R.J. Umberger, a Pittsburgh native, fired a shot off Fleury that Pahlsson knocked in for a 2-0 lead. The goal was reviewed on replay.
Nash assisted on the third goal with a floating pass from the neutral zone that a hustling Voracek chased down and flipped past a diving Fleury to all but wrap up the victory.
Mason was fantastic in net, making glove saves look easy.
Vermette stuck with the puck around the net and knocked in his own rebound late in the third for his 13th goal and a 4-1 lead.
Notes: Kunitz has 18 goals and the Penguins are 12-2-1 when he scores. ... Penguins coach Dan Bylsma has 99 career wins, one shy of becoming the third coach in team history to reach 100.